Showing papers on "B vitamins published in 1997"

Plasma Total Homocysteine, B Vitamins, and Risk of Coronary Atherosclerosis

Abstract: Epidemiological research has shown that elevated plasma total homocysteine (tHcy) is a risk factor for atherosclerotic disease. In the present case-control study, we investigated whether fasting or postmethionine-loading tHcy was a stronger predictor of risk of severe coronary atherosclerosis. Furthermore, we studied levels of B vitamins, which are involved in homocysteine metabolism. Subjects were recruited from men and women, aged 25 to 65 years, who underwent coronary angiography between June 1992 and June 1994 in a hospital in Rotterdam, The Netherlands. Cases (n=131) were defined as those with > or =90% occlusion in one and > or =40% occlusion in a second coronary artery, while control subjects (n=88) had <50% occlusion in only one coronary vessel. In addition, a population-based control group free from clinical cardiovascular disease (n=101) was studied. Coronary patients were studied at least 2.5 months after angiography or other acute illness, such as myocardial infarction. After adjusting for age and sex differences between the groups, cases had 9% (P=.01) higher geometric mean fasting and 7% (P=.04) higher geometric mean postload tHcy than the combined control groups. Despite higher levels of tHcy for cases, their geometric mean levels of red cell folate and pyridoxal 5'-phosphate were higher than for control subjects, whereas plasma vitamin B12 was only slightly lower in cases. The frequency distribution of tHcy values in cases was slightly shifted toward the right, across the entire range, compared with the distribution in the combined control group. This was somewhat more obvious for fasting than postload tHcy levels. The odds ratio (OR) for severe coronary atherosclerosis (case status) for each 1 SD increase in fasting tHcy (5 micromol/L) was 1.3 (95% confidence interval [CI], 1.0-1.6), similar to the OR for each 1 SD increase (12 micromol/L) in postmethionine-loading tHcy (1.3 [95 CI, 1.0-1.7]), after adjustment for sex, age, and other potential confounders. Furthermore, there was a significant linear trend of increasing fasting tHcy with increasing number of occluded arteries (P=.01), correcting for sex, age, and other potential confounders. Our data show a positive association between plasma tHcy and risk of severe coronary atherosclerosis, of similar strength for fasting and postload tHcy levels. The data suggest that the association exists over a wide range of tHcy levels, without a clear cutoff point below which there is no increased risk.

Interaction of IgA with Fc alpha receptors of human mesangial cells activates transcription factor nuclear factor-kappa B and induces expression and synthesis of monocyte chemoattractant protein-1, IL-8, and IFN-inducible protein 10.

Abstract: The mechanisms of glomerular damage in IgA nephropathy remain undefined. Mesangial cells (MC) possess Fc receptors for IgA (Fc alpha R), and their occupancy triggers cytokine expression, cell proliferation, and extracellular matrix synthesis. In cultured human MC we examined the effects of soluble IgA aggregates (AIgA) on the activation of nuclear factor-kappa B (NF-kappa B) and the production of proinflammatory chemokines monocyte chemoattractant protein-1 (MCP-1), IL-8, and IFN-inducible protein-10 (IP-10). The exposure of MC to AIgA rapidly activated a NF-kappa B complex constituted of p50 and p65 subunits. NF-kappa B activation was dose dependent, abolished by preincubation with IgA Fc fragments (indicating that AIgA effects occur via specific Fc alpha R), and attenuated by kinase inhibitors. MC stimulation with AIgA increased the mRNA expression of MCP-1, IL-8, and IP-10 in a time- and dose-dependent manner. Maximal expression of IL-8 was observed at 3 h (4.5-fold), while IP-10 and MCP-1 peaked at 6 h (5-fold for both). AIgA also induced biosynthesis and release of the chemokines, which presented biological activity in neutrophil and monocyte chemoattractant assays, peaking at 6 and 9 h, respectively. MC pretreatment with the antioxidant pyrrolidine dithiocarbamate inhibited NF-kappa B activation and chemokine mRNA expression. This study shows that stimulation of Fc alphaR in MC induces gene expression of MCP-1, IL-8, and IP-10, a process partially mediated by NF-kappa B activation. These data may be of importance for a better understanding of the pathogenesis of glomerular damage in IgA immune complex-related diseases.

Intake of selected micronutrients and risk of colorectal cancer.

Abstract: The relationship between various micronutrients and colorectal cancer risk was investigated using data from a case-control study conducted between January 1992 and June 1996 in Italy. Cases were 1,953 incident, histologically confirmed colorectal cancers (1,225 of the colon and 728 of the rectum), admitted to the major teaching and general hospitals in the study areas, and 4,154 controls with no history of cancer, admitted to hospitals in the same catchment areas for acute, non-neoplastic diseases unrelated to the digestive tract and requiring no long-term modifications of the diet. Dietary habits were investigated using a validated food-frequency questionnaire. Odds ratio (ORs) were computed after allowance for age, sex and other potential confounding factors, including physical activity, total energy and fibre intake. For most micronutrients, ORs were below unity with increasing quintile of intake. The most consistent protective effects were for carotene, riboflavin and vitamin C (Multivariate ORs from the continuous model, with unit set as the difference between the upper cut-point of the 4th quintile and that of the 1st one, were 0.65, 0.73 and 0.80, respectively). Inverse relationships were observed also for calcium and vitamin D (ORs of 0.85 and 0.93, respectively). When the combined effect of calcium and vitamin D and selected anti-oxidants was considered, the OR reached 0.46 in subjects reporting high calcium/vitamin D and high anti-oxidant intake compared to those reporting low intake of both groups of micronutrients. Most results were apparently stronger for colon cancer and among females. Our results provide further support for a protective effect of several micronutrients on colorectal cancer risk and some indications for a specific and stronger effect of selected anti-oxidants.

Treatment of Hyperhomocysteinemia in Renal Transplant Recipients: A Randomized, Placebo-Controlled Trial

Abstract: Background: Stable renal transplant recipients have an excess prevalence of hyperhomocysteinemia, which is a risk factor for arteriosclerosis. Objective: To determine the effect of treatment with 1) vitamin B 6 or 2) folic acid plus vitamin B 12 on fasting and post-methionine-loading plasma total homocysteine levels in renal transplant recipients. Design: Block-randomized, placebo-controlled, 2 x 2 factorial study. Setting: University-affiliated transplantation program. Patients: 29 clinically stable renal transplant recipients. Intervention: Patients were randomly assigned to one of four regimens: placebo (n = 8); vitamin B 6 , 50 mg/d (n = 7); folic acid, 5 mg/d, and vitamin B 12 , 0.4 mg/d (n = 7); or vitamin B 6 , 50 mg/d, folic acid, 5 mg/d, and vitamin B 12, 0.4 mg/d (n = 7). Measurements: Fasting and 2-hour post-methionine-loading plasma total homocysteine levels. Results: Vitamin B 6 treatment resulted in a 22.1% reduction in geometric-mean post-methionine-loading increases in plasma total homocysteine levels (P = 0.042), and folic acid plus vitamin B 12 treatment caused a 26.2% reduction in geometric-mean fasting plasma total homocysteine levels (P = 0.027). These results occurred after adjustment for age; sex; and pretreatment levels of total homocysteine, B vitamins, and creatinine. Conclusions: Vitamin B 6 should be added to the combination of folic acid and vitamin B 12 for effective reduction of both post-methionine-loading and fasting plasma total homocysteine levels in renal transplant recipients.

Evaluation of multiple micronutrient supplementation in the management of oral submucous fibrosis in Karachi, Pakistan.

Abstract: Oral submucous fibrosis (OSF) is an oral precancerous condition characterized by symptoms such as intolerance to spicy food, altered salivation, progressive difficulty in opening the mouth, and signs like vesiculation, ulceration, blanching, rigidity, and stiffening of the oral mucosa and depapillation and altered mobility of the tongue. It is seen mostly among people of Indian subcontinent origin. The major structural change is extensive fibroelastic scarring of the lamina propria and deeper connective tissues. A combination of micronutrients (vitamins A, B complex, C, D, and E) and minerals (iron, calcium, copper, zinc, magnesium, and others) was evaluated for its efficacy in controlling the symptoms and signs of OSF in 117 compliant subjects in Karachi, Pakistan, in a single-arm preliminary study. The subjects received supplementation for one to three years. Significant improvement in symptoms, notably intolerance to spicy food, burning sensation, and mouth opening, was observed at exit. The interincisor distance deteriorated in 11 subjects (10%) at exit; it was stable in 56 subjects (49%) and improved in 48 (41%). The mean interincisor distance was 19.1 +/- 10.8 (SD) mm at exit compared with 16.2 +/- 7.5 mm at baseline. A significant proportion of concomitant lesions like leukoplakia also regressed at exit. The major outcome from this study was a beneficial clinical response in subjects with OSF to multiple micronutrient intervention, which justifies its further evaluation in well-designed randomized controlled trials in other settings in South Asia.

The neurological syndrome of infantile cobalamin deficiency: Developmental regression and involuntary movements

Abstract: Developmental regression is the presenting symptom of most infants with cobalamin (Vitamin B12) deficiency. We present a report of three infants with cobalamin deficiency in which the infants also developed a movement disorder. In each case the mother was a vegetarian and the infant was exclusively breast-fed. In two of the infants, a striking movement disorder consisting of a combination of tremor and myoclonus particularly involving face, tongue, and pharynx appeared 48 h after the initiation of treatment with intramuscular cobalamin. This was associated with marked changes in plasma amino acid levels. Paradoxically, the onset of the movement disorder coincided with overall neurological improvement. The third infant had a persistent focal tremor, which appeared before the commencement of treatment. The movements slowly abated during a 3-6 week period. The presence of a movement disorder in cobalamin deficiency has received less attention than other features, but in a mild form is probably common. It may offer an early clue to the diagnosis before the onset of profound neurological deterioration. The cause of the severe movement disorder that can appear after treatment is not known.

Diagnosis of cobalamin deficiency: the old and the new

Abstract: Once upon a time we thought that we knew how to diagnose cobalamin (Cbl) deficiency. It started with a patient. He, or more often she, lacked energy. If you were lucky she might have a sore mouth and a smooth tongue and even some pinsand-needles sensation in fingers and/or toes. But the main pointer came with the blood count which, in the absence of thalassaemia trait, showed macrocytosis in almost all patients, usually with other abnormalities in the blood. Almost half a century of experience led us oldies to believe that the serum Cbl level was low in every patient with Cbl deficiency who had normal Cbl plasma binders. A megaloblastic marrow, abnormal Cbl absorption tests and an optimal response to Cbl therapy unless there was a good reason for it being otherwise, completed the diagnosis of the common disorder producing Cbl deficiency, namely, pernicious anaemia (PA). However, we are now told that significant Cbl deficiency not infrequently occurs in the presence of a normal blood picture and that the serum Cbl level need not be low. These statements are quoted as fact in almost all publications on the newer diagnostic methods (Wickramasinghe, 1995). If these claims are unsubstantiated a serious disservice is being done and unecessary treatment is being given to many patients. Bone marrow aspirations nowadays are rarely done merely to establish megaloblastosis, and, although we do not necessarily agree, we will not quibble as patients do not like the procedure. Nevertheless, when attempting to introduce new diagnostic methods, absence of information as to whether haemopoiesis is megaloblastic or not and the inability to do a deoxyuridine suppression test if the bone marrow aspiration has been omitted, makes it even more difficult to interpret new data. New versions of Cbl absorption tests now seem to be acceptable if the old ones do not give the required answers. One does not even need patients; most publications in the last decade are concerned with examination of serum samples. Any old serum is still good; even those languishing in the freezer for 30 years. These sera are examined for methylmalonic acid (MMA) and/or for homocysteine (Hcy), and if these are raised, we are told, there is a considerable likelihood that the serum belongs to a patient with Cbl deficiency. Indeed, among 406 sera 98·4% were diagnosed as coming from patients with Cbl deficiency (Savage et al, 1994). A challenge to entrenched ideas is welcome in every sphere if problems are to be resolved and old baggage thrown out. The purpose of these comments is to examine critically the newer developments in diagnosis of Cbl deficiency and whether the new claims have indeed invalidated that which most of us have accepted as correct.

Consequences of Hyperhomocyst(e)inemia on Vascular Function in Atherosclerotic Monkeys

Abstract: Moderate elevation of plasma homocyst(e)ine is associated with increased risk for atherosclerotic vascular disease. In a previous study, we observed impaired vascular function in nonatherosclerotic monkeys with moderate hyperhomocyst(e)inemia. In this study, we tested the hypothesis that dietary intervention to lower plasma homocyst(e)ine corrects vascular dysfunction in atherosclerotic monkeys. Cynomolgus monkeys were fed an atherogenic diet that produces both hypercholesterolemia and moderate hyperhomocyst(e)inemia. After 17 months, the atherogenic diet was supplemented with B vitamins (5 mg folic acid, 400 micrograms vitamin B-12, and 20 mg vitamin B-6 daily) for 6 months. Total plasma homocyst(e)ine decreased from 12.8 +/- 2.8 to 3.5 +/- 0.3 mumol/L (n = 9; mean +/- SE; P .05). In response to intra-arterial infusion of collagen, blood flow to the leg decreased by 30 +/- 3% and 38 +/- 5%, respectively, before and after vitamin supplementation (P > .05). In vivo responses of resistance vessels to endothelium-dependent vasodilators (acetylcholine or ADP) were impaired at baseline and did not improve after vitamin supplementation. In carotid artery studied ex vivo, relaxation to low doses of acetylcholine improved after vitamin supplementation, but maximal relaxation remained impaired. Ex vivo thrombomodulin anticoagulant activity was threefold higher in monkeys fed the atherogenic diet (with or without B vitamins) than in normal monkeys (P < .05). We conclude that normalization of plasma homocyst(e)ine is insufficient to restore normal vascular function in atherosclerotic monkeys with persistent hypercholesterolemia and that atherosclerosis, with or without hyperhomocyst(e)inemia, is associated with elevated thrombomodulin activity.

Evaluation of the efficacy of thiamine and pyridoxine in the treatment of symptomatic diabetic peripheral neuropathy

Abstract: The clinical response to therapeutic doses of two vitamins were determined in diabetic patients with symptomatic peripheral neuropathy. Of 200 consecutive patients, 100 were randomly allocated to treatment with both thiamine (25 mg/day) and pyridoxine (50 mg/day) group A and the rest group B to treatment with an identical tablet containing 1 mg/day each of thiamine and pyridoxine. Pain, numbness, paraesthesia and impairment of sensation and ankle in the legs were graded into none, mild, moderate or severe. Blood thiamine levels were measured using HPLC fluorimetry. Four weeks after starting treatment the grade was less than on the first visit in 88.9%, 82.5% and 89.7% of those whose worst symptoms were pain, numbness and paraesthesia respectively for group A compared with 11.1%, 40.5% and 39.4% respectively for group B. The severity of signs of peripheral neuropathy decreased in 48.9% of patients in group A compared with 11.4% in group B. The mean (s.e.) pre-treatment whole blood thiamine levels decreased with increasing severity of symptoms: 64.2 (2.81), 57.7 (3.25) and 52.2 (2.14) micrograms/l for those with mild, moderate and severe symptoms respectively (analysis of variance, p = 0.03). Diabetic peripheral neuropathy in Dar es Salaam is associated with thiamine deficiency. Dietary guidelines for diabetic patients should emphasize a balanced diet.

Low Concentrations of Folate in Serum and Erythrocytes of Smokers: Methionine Loading Decreases Folate Concentrations in Serum of Smokers and Nonsmokers

Abstract: Recent data suggest that hyperhomocysteinemia is associated with an increased risk for premature vascular disease. Total plasma homocysteine (tHcy) may be increased by impaired activity of enzymes or suboptimal availability of B vitamins (1). Homocysteine transsulfuration reactions are catalyzed by the enzymes cystathionine β-synthase and cystathionine lyase in the presence of coenzyme vitamin B6, and remethylation of homocysteine is performed by the enzymes methionine synthase and betaine-homocysteine methyltransferase with vitamin B12 as a coenzyme for the former enzyme. 5-Methyltetrahydrofolate (5-methylTHF) or betaine are methyl donors during remethylation. The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) with coenzyme FADH2 synthesizes 5-methyl-THF from 5,10-methylenetetrahydrofolate (5,10-MTHF) (2). The postmethionine load (PML) abnormal tHcy increments may reflect suboptimal plasma vitamin B6 or deficiency of cystathionine β-synthase (3). The present report describes the effects of methionine loading on serum and erythrocyte folate, tHcy, and related thiols in smokers and nonsmokers. We recruited 63 apparently healthy smokers [ages 37.8 ± 0.8 years; body mass index (BMI), 25.4 ± 0.5; male/female, 39/24; cigarettes/day, 16.2 ± 0.8; smoking period (years), 19.7 ± 0.7], 44 nonsmokers (ages 37.8 ± 1.0 years; BMI, 24.5 ± 0.5; male/female, 26/18), and 23 former smokers who refrained from smoking for ≥3 months …

B-complex vitamins in the prophylaxis and treatment of Wernicke-Korsakoff syndrome

Abstract: Wernicke-Korsakoff syndrome, which is associated with high morbidity and mortality, is a more common neuropsychiatric sequela of alcohol misuse than is widely realized It is easily prevented and treated with parenteral B-complex vitamins, although this treatment is widely under-utilized

Carbogen and nicotinamide in the treatment of bladder cancer with radical radiotherapy.

Abstract: Carbogen and nicotinamide have been evaluated in a phase II study as hypoxia-modifying agents during radical radiotherapy for bladder cancer using a standard daily 20-fraction schedule. Three groups of patients have received (a) nicotinamide alone, given orally in a dose of 80 mg kg(-1) daily with 52.5 Gy in 20 fractions over 4 weeks, (b) carbogen alone, with 50 Gy in 20 fractions over 4 weeks, and (c) carbogen and nicotinamide, with 50-52.5 Gy in 20 fractions over 4 weeks. Ten patients were treated in each group. All patients completed carbogen and radiotherapy as prescribed, but only 45% completed daily nicotinamide over the 4-week treatment period. The end points of this study were acute bowel and bladder morbidity and local control at cystoscopy 6 months after treatment. An expected level of acute bowel and bladder morbidity was seen that reverted to normal in most patients by 12 weeks with no difference between the three treatment groups. Complete response rates at 6 months were seven out of ten (100%) in the nicotinamide alone group, nine out of ten (90%) in the carbogen alone group and seven out of ten (70%) in the carbogen and nicotinamide group. It is concluded that carbogen and nicotinamide may improve the results of daily fractionated radiotherapy in bladder cancer and that further evaluation is required.

Iatrogenic Wernicke's encephalopathy in allogeneic bone marrow transplantation: a study of eight cases.

Abstract: Wernicke's encephalopathy (WE) is a neuropsychiatric condition generally caused by acute thiamine deficiency and classically involves the triad of altered mentation, ataxia and ophthalmoplegia. It is most common among alcoholics, but several other causes have been identified, including total parenteral nutrition (TPN) use. We present eight cases of WE in patients undergoing allogeneic BMT, where thiamine deficiency was caused by a lack of vitamin supplementation during TPN administration. Clinically, WE presented as a severe refractory metabolic acidosis, preceded by 'raspberry tongue', and ophthalmologic and neurologic dysfunction. The sites most affected were the periventricular structures and the thalamus, and no mammilary bodies lesions were found.